title: Myosin phosphatase isoforms as determinants of smooth muscle contractile function and calcium sensitivity of force production.
abstract: The dephosphorylation of myosin by the MP causes smooth muscle relaxation. MP is also a key target of signals that regulate vascular tone and thus blood flow and pressure. Here, we review studies from the past two decades that support the hypothesis that the regulated expression of MP subunits is a critical determinant of smooth muscle responses to constrictor and dilator signals. In particular, the highly regulated splicing of the regulatory subunit Mypt1 Exon 24 is proposed to tune sensitivity to NO/cGMP-mediated relaxation. The regulated transcription of the MP inhibitory subunit CPI-17 is proposed to determine sensitivity to agonist-mediated constriction. The expression of these subunits is specific in the microcirculation and varies in developmental and disease contexts. To date, the relationship between MP subunit expression and vascular function in these different contexts is correlative; confirmation of the hypothesis will require the generation of genetically engineered mice to test the role of MP subunits and their isoforms in the specificity of vascular smooth muscle responses to constrictor and dilator signals.
authors.affiliation: Department of Medicine (Cardiology), University of Maryland Baltimore, Baltimore, Maryland, USA.
authors.forename: Rachael P
authors.initials: RP
authors.lastname: Dippold
authors.forename: Steven A
authors.initials: SA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D055806:Microvessels / Q000201:enzymology / Q000502:physiology; D008955:Models, Cardiovascular; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins; D021122:Protein Subunits; D015398:Signal Transduction; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D009124:Muscle Proteins; D010750:Phosphoproteins; C491520:Ppp1r14a protein, mouse; D021122:Protein Subunits; D009219:Myosin-Light-Chain Kinase; D043263:Myosin-Light-Chain Phosphatase; C510645:Ppp1r12a protein, mouse
keywords: CPI-17; Mypt1; NO; PKG1; cGMP; myosin phosphatase; vascular smooth muscle